Mass Spectrometric Analysis of Peptides Associated with the Human Class I MHC Molecules HLA-A2.1 and HLA-B7 and Identification of Structural Features that Determine Binding

2015 ◽  
pp. 39-62 ◽  
Author(s):  
Victor H. Engelhard ◽  
Ettore Appella ◽  
David C. Benjamin ◽  
Wanda M. Bodnar ◽  
Andrea L. Cox ◽  
...  
Keyword(s):  
Structural Features ◽  
Mass Spectrometric ◽  
Mass Spectrometric Analysis ◽  
Class I ◽  
Spectrometric Analysis ◽  
Human Class ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Hla A2.1

scholarly journals Bap31 Enhances the Endoplasmic Reticulum Export and Quality Control of Human Class I MHC Molecules

2006 ◽  
Vol 177 (9) ◽  
pp. 6172-6181 ◽  
Author(s):  
John J. Ladasky ◽  
Sarah Boyle ◽  
Malini Seth ◽  
Hewang Li ◽  
Tsvetelina Pentcheva ◽  
...  
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Class I ◽  
Human Class ◽  
Class I Mhc ◽  
Mhc Molecules

scholarly journals Restricted MHC–peptide repertoire predisposes to autoimmunity

2005 ◽  
Vol 202 (1) ◽  
pp. 73-84 ◽  
Author(s):  
Nadezda N. Logunova ◽  
Christophe Viret ◽  
Leonid A. Pobezinsky ◽  
Sara A. Miller ◽  
Dmitri B. Kazansky ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Mhc Class Ii ◽  
Selective Advantage ◽  
Class Ii ◽  
Structural Features ◽  
Peptide Ligands ◽  
Class I ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Single Complex

MHC molecules associated with autoimmunity possess known structural features that limit the repertoire of peptides that they can present. Such limitation gives a selective advantage to TCRs that rely on interaction with the MHC itself, rather than with the peptide residues. At the same time, negative selection is impaired because of the lack of negatively selecting peptide ligands. The combination of these factors may predispose to autoimmunity. We found that mice with an MHC class II–peptide repertoire reduced to a single complex demonstrated various autoimmune reactions. Transgenic mice bearing a TCR (MM14.4) cloned from such a mouse developed severe autoimmune dermatitis. Although MM14.4 originated from a CD4+ T cell, dermatitis was mediated by CD8+ T cells. It was established that MM14.4+ is a highly promiscuous TCR with dual MHC class I/MHC class II restriction. Furthermore, mice with a limited MHC–peptide repertoire selected elevated numbers of TCRs with dual MHC class I/MHC class II restriction, a likely source of autoreactivity. Our findings may help to explain the link between MHC class I responses that are involved in major autoimmune diseases and the well-established genetic linkage of these diseases with MHC class II.

Comparison of the capacity of murine and human class I MHC molecules to stimulate T cell activation

1992 ◽  
Vol 144 (2) ◽  
pp. 392-406 ◽  
Author(s):  
Hanan Gur ◽  
Mary C. Wacholtz ◽  
Wen-Rong Lie ◽  
Peter E. Lipsky ◽  
Thomas D. Geppert
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Class I ◽  
Human Class ◽  
Class I Mhc ◽  
Mhc Molecules

scholarly journals Presentation of Cytosolic Glycosylated Peptides by Human Class I Major Histocompatibility Complex Molecules in Vivo

1999 ◽  
Vol 190 (1) ◽  
pp. 145-150 ◽  
Author(s):  
John S. Haurum ◽  
Ingelise Bjerring Høier ◽  
Gemma Arsequell ◽  
Anne Neisig ◽  
Gregorio Valencia ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Posttranslational Modifications ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Major Histocompatibility ◽  
Human Class ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Histocompatibility Complex

Antigens presented by class I major histocompatibility complex (MHC) molecules for recognition by cytotoxic T lymphocytes consist of 8–10-amino-acid-long cytosolic peptides. It is not known whether posttranslationally modified peptides are also presented by class I MHC molecules in vivo. Many different posttranslational modifications occur on cytoplasmic proteins, including a cytosolic O-β-linked glycosylation of serine and threonine residues with N-acetylglucosamine (GlcNAc). Using synthetic glycopeptides carrying the monosaccharide O-β-GlcNAc substitution on serine residues, we have shown that glycopeptides bind efficiently to class I MHC molecules and elicit a glycopeptide-specific cytotoxic T lymphocyte response in mice. In this study, we provide evidence that peptides presented by human class I MHC molecules in vivo encompass a small, significant amount of glycopeptides, constituting up to 0.1% of total peptide. Furthermore, we find that carbohydrate structures present on glycopeptides isolated from class I MHC molecules are dominated by the cytosolic O-β-GlcNAc substitution, and synthetic peptides carrying this substitution are efficiently transported by TAP (transporter associated with antigen presentation) into the endoplasmic reticulum. Thus, in addition to unmodified peptides, posttranslationally modified cytosolic peptides carrying O-β-linked GlcNAc can be presented by class I MHC molecules to the immune system.

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